Velocardiofacial Syndrome

Definition of Velocardiofacial Syndrome

Velocardiofacial syndrome abbreviated as  and is considered to be one among the most common syndromes involving some multiple anomalies among human beings.

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Other names used to refer to VCFS are DiGeorge Syndrome, 22q11.2 deletion syndrome, autosomal dominant Opitz G/BBB syndrome, Cayler Cardiofacial syndrome, Conotruncal Anomaly Face syndrome (CTAF), Shprintzen syndrome, Sedlackova syndrome, thymic hypoplasia or congenital thymic aplasia.

VCFS is usually characterized by an association or a combination of a lot of medical problems which may vary from one child to another. VCFS has been known to approximately affect 1 newborn among 4,000 newborn babies.

It has greater chances to affect a greater number of individuals in the sense that those with the 22q11.2 deletion of a small part of the defective gene may not be properly diagnosed or not being assessed earlier due to the limited clinical manifestations of symptoms.

Symptoms of Velocardiofacial Syndrome

The clinical features of VCFS greatly vary among patients, even if they belong to the same family and it affects a lot of body parts.

The characteristic symptoms include:

• Birth defects such as a congenital heart problem that is of the conotruncal type such as the interrupted aortic arch, cases of truncus arteriosus and tetralogy of Fallot
• Palatal problems that predispose the child to difficulties of feeding and speech
• Similar facial features like having an almond-shaped eyes, elongated face, wide nose and small size of ears
• Impaired thymic development that predisposes a child to be at increased risk for infections or to have an autoimmunity
• Learning disabilities and overt developmental delay
• Vision problems such as bilateral cataracts, small optic discs, posterior embryotoxon and tortous retinal vessels
• Congenital absence of nasolacrimal duct
• Hypocalcemia related to hypoparathyroidism
• Immune deficiency making it difficult to fight against infections
• Thymic aplasia
• Middle ear infections
• Structural and functional abnormalities of the kidneys with kidney defects
• Muscles tend to be weak with musculoskeletal defects
• Spinal differences such as in the curvature like in cases of scoliosis
• Bony abnormalities located in the neck or upper back
• Tapered fingers
• Psychiatric disorders among adult patients such as developing depression, schizophrenia and anxiety disorders

Causes of Velocardiofacial Syndrome

The cause of VCFS is mainly due to a genetic microdeletion that occurs from the loss of a small portion of the genetic material q11.2 band which is located on one of the long arm of the two 22nd chromosomes of a patient. The exact mechanism that leads to all of its associated features is still unknown. This syndrome involves migration defects of the neural crest cells as well as the early development of branchial arches.

Diagnosis of Velocardiofacial Syndrome

VCFS is suspected in an individual based on presenting symptoms. Diagnosis is made utilizing a submicroscopic deletion of chromosome 22 which are detected through the following:

• Fluorescence in situ hybridization (FISH) which is done on a blood sample using one DNA probe each time from the defective 22q11.2 chromosomal region
• BACs-on-Beads technology where multiple probes are used simultaneously from the 22q11.2 region
• Multiplex ligation-dependent probe amplification (MLPA) where various probes are used to identify microdeletions for selected regions of 22q11.2
• Array-comparative genomic hybridization (array-CGH) where molecular karyotype is used with a large number of probes to screen the entire genome for any presence deletions or duplications; and evaluates the symptoms and prognosis of VCSF
• Genetic testing to assess and evaluate the clinical course and prenatal testing of the presence of 22q11.2 deletion syndrome

Treatment of Velocardiofacial Syndrome

There is no known cure for VCFS or the 22q11.2 deletion syndrome. Individual features are managed on a case to case basis by attending physicians using some standard treatments available.

Clinical management is dependent on a patient’s age together with acute medical problems such as:

• Newborns are admitted in the hospital for work-up of a heart problem and feeding problem,
• Infancy and preschool years to manage for cleft palate, feeding difficulties, and developmental disorders
• School years focuses to manage on cognitive, learning disorders and behavioral problems of the child
• Late adolescence and adult years is more of managing some psychiatric problems like schizophrenia or any bipolar disorder

Specific treatments are:

• Cardiac surgery for congenital cardiac abnormalities
• Thymus transplant for thymus absence
• Cleft palate repair
• Vitamin D and calcium supplements for hypocalcemia associated with hypothyroidism
• Antibiotics for bacterial infections
• Blood transfusion and immunization with live vaccines with some special precautions for immune problems

Life expectancy of Velocardiofacial Syndrome

There is no sufficient data yet to determine the specific life span among patients with VCFS although some studies generalize those individuals who live until their early adult years without serious health concerns can live a normal life span.

Pictures

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Image 3 Source – www.specialchild.com

References:

1. http://emedicine.medscape.com/article/892655-overview
2. https://www.genome.gov/25521139
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805186/
4. Tarquinio DC, Jones MC, Jones KL, Bird LM (2012 Nov). Growth charts for 22q11 deletion syndrome. Am J Med Genet A. 158A (11):2672-81.
5. Zemble R, Luning Prak E, McDonald K, McDonald-McGinn D, Zackai E, Sullivan K (2010 Sep). Secondary immunologic consequences in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Immunol. 136 (3):409-18.
6. Eberle P, Berger C, Junge S, et al (2009 Feb). Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11.2 microdeletion and partial DiGeorge syndrome. Clin Exp Immunol. 155 (2):189-98.